Project Summary Periodontal disease is one of the major causes of tooth loss in the world. Although psychological stress is known to aggravate periodontal pathology, the exact mechanisms remain to be elucidated. Studies from our laboratory have shown that psychological stress decreases available oxygen and increases opportunistic bacteria during cutaneous wound healing. Hyperoxia therapy in the stressed animals was able to restore healing to control levels. Previous studies have also shown decreased oxygenation of the tissues during periodontitis, and hyperbaric oxygen therapy to be of benefit in its treatment. Lower tissue oxygen levels could decrease immune potential, and favor the growth of anaerobic bacteria that have been associated with periodontal pathology. With approximately 30% of the adult US population suffering from periodontal disease, and with stress more prevalent than ever, understanding this association is important. Hence, the long-term goal of our study is to elucidate the molecular mechanisms underlying periodontal pathology in psychological stress. This proposal aims to explore the role of altered tissue oxygenation in periodontal pathology. Our central hypothesis is that psychological stress increases periodontal pathology by decreasing oxygen availability in the periodontal tissues. We intend to study our hypothesis using a rat model of periodontitis. Our objectives are to determine if: 1) psychological stress decreases wound oxygenation in periodontal tissues and 2) restoring oxygenation to the hypoxic periodontal tissues, by hyperoxia therapy, would alleviate the effects of stress on periodontitis. Tissue hypoxia will be evaluated by immunohistochemistry using a hypoxia marker (pimonidazole), and corroborated with studies of hypoxia inducible factor (HIF) activation. These values will be correlated to the periodontal status of the respective tissues. As with our previous stress-inflammatory model of impaired wound healing, we anticipate to decrease periodontal pathology by restoring oxygenation to the tissues. A better understanding of the role of stress in periodontal disease will help enhance existing treatment modalities, and guide evidence based alternatives for patient care. Future studies will plan to investigate the role of oxygen regulated enzymes and genes, as well as glucocorticoid and catecholaminergic pathways. This will give us new insight into the mechanisms of how stress affects periodontal disease. Project Narrative: Periodontal disease is one of the major causes of tooth loss in the world. Psychological stress is known to increase the severity of periodontal disease. In this proposal, we explore the role of decreased tissue oxygenation in periodontal pathology in the context of stress. Results from these studies will provide valuable insight into the role of oxygen in stress-induced periodontal pathology and its ability to ameliorate it, leading to future studies in oxygen regulated pathways. The insights gain will help take our findings from the bench to the clinics, and to develop novel strategies to improve healing and promote periodontal health.